Mass Spectrometry Imaging Differentiates Chromophobe Renal Cell Carcinoma and Renal Oncocytoma with High Accuracy.

While subtyping of the majority of malignant chromophobe renal cell carcinoma (cRCC) and benign renal oncocytoma (rO) is possible on morphology alone, additional histochemical, immunohistochemical or molecular investigations are required in a subset of cases. As currently used histochemical and immunohistological stains as well as genetic aberrations show considerable overlap in both tumors, additional techniques are required for differential diagnostics. Mass spectrometry imaging (MSI) combining the detection of multiple peptides with information about their localization in tissue may be a suitable technology to overcome this diagnostic challenge.

Aberrant Expression of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) in Warthin Tumors.

The Warthin tumor represents the second most frequent benign tumor of the parotid gland and is characterized by the presence of oncocytes rich in structurally and functionally altered mitochondria. Next to its role in metabolism, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is also implicated in cellular mitophagy. Immunohistochemistry was carried out on Warthin tumor and normal control (parotid gland with striated ducts) tissues, using anti-GAPDH specific antibodies followed by digital image analysis.

CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma.

The transcription factor cAMP response element-binding protein (CREB1) has been shown to be involved in diverse biological pathways including the regulation of cell proliferation, apoptosis, cell cycle progression, and metastasis. In this context, aberrant expression of CREB1 and the functional consequences are well investigated in a number of hematopoietic and solid tumors. However, CREB1 expression and underlying control mechanisms are only poorly analyzed in renal cell carcinoma (RCC).

Metastatic squamous cell carcinoma of colon from esophageal cancer.

Background: Esophageal cancer including squamous cell carcinoma (SCC) and adenocarcinoma represents 4% of all cancers in the United States. Patients with esophageal cancer frequently present with locally advanced disease, and about 40% of patients have evidence of metastatic disease on presentation. Common sites of metastasis include liver, lung and bone.

HLA-E expression and its clinical relevance in human renal cell carcinoma.

The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and -C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance.While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity.

Identification of novel microRNAs regulating HLA-G expression and investigating their clinical relevance in renal cell carcinoma.

The non-classical human leukocyte antigen G (HLA-G) is expressed at a high frequency in renal cell carcinoma (RCC) and is associated with a higher tumor grade and a poor clinical outcome. This might be caused by the HLA-G-mediated inhibition of the cytotoxicity of T and NK cells. Therefore a selective targeting of HLA-G might represent a powerful strategy to enhance the immunogenicity of RCC lesions.

The Microphthalmia-Associated Transcription Factor p.E318K Mutation Does Not Play a Major Role in Sporadic Renal Cell Tumors from Caucasian Patients.

Objective: The transcription factor MITF (microphthalmia-associated transcription factor) is known to induce expression of hypoxia-inducible factor (HIF1-α), which is involved in renal carcinogenesis. The MITF p.E318K mutation leads to deficient SUMOylation of MITF, resulting in enhanced activation of its target genes.

Homozygous G/G variant of SNP309 in the human MDM2 gene is associated with earlier tumor onset in Caucasian female renal cell carcinoma patients.

Human mouse double minute 2 (Mdm2) plays an essential role in the regulation of the tumor suppressor p53. The G/G variant of SNP309 was shown to increase Mdm2 mRNA/protein expression and to be associated with an increased risk and earlier onset of different cancers in Asian populations. However, the frequency and impact of these G/G variants have not been studied in Caucasian renal cell carcinoma (RCC) patients.

Clinical relevance of miR-mediated HLA-G regulation and the associated immune cell infiltration in renal cell carcinoma.

In human tumors of distinct origin including renal cell carcinoma (RCC), the non-classical human leukocyte antigen G (HLA-G) is frequently expressed, thereby inhibiting the cytotoxic activity of T and natural killer (NK) cells. Recent studies demonstrated a strong post-transcriptional gene regulation of the HLA-G by miR-152, -148A, -148B and -133A. Standard methods were applied to characterize the expression and function of HLA-G, HLA-G-regulatory microRNAs (miRs) and the immune cell infiltration in 453 RCC lesions using a tissue microarray and five RCC cell lines linking these results to clinical parameters.

Functional analyses and prognostic significance of SFRP1 expression in bladder cancer.

Purpose: We previously showed that the Wnt-signaling antagonist SFRP1 (secreted frizzled-related protein 1) is a promising marker in bladder cancer. The aim of this study was to validate the prognostic role and analyze the functional significance of SFRP1.

Methods: Four bladder cancer cell lines (RT112, RT4, J82 and BFTC905) and one urothelial cell line (UROtsa) were used for functional characterization of SFRP1 expression.

Mdm2 SNP309 G-variant is associated with invasive growth of human urinary bladder cancer.

Objective: Human mouse double minute 2 (Mdm2) is essential in degrading p53 by acting as an ubiquitin ligase and therefore plays a vital role in cell cycle and survival. The G-variant of the Mdm2 SNP309, which is located within the promoter of the Mdm2 gene, increases expression of Mdm2 and thereby inhibits the p53 pathway. Several studies have investigated the influence of this SNP on disease risk and onset of various malignancies.

Comparative expression profiling for human endoplasmic reticulum-resident aminopeptidases 1 and 2 in normal kidney versus distinct renal cell carcinoma subtypes.

Altered expression of the ER-resident aminopeptidases ERAP1 and ERAP2 might play an important role in shaping the MHC class I-presented peptide repertoire, but their function in tumors has not been determined in detail. Thus, the expression of ERAP1, ERAP2 and HLA class I heavy chain (HC) was analysed in various renal tumor types and corresponding kidney parenchyma by immunohistochemistry. Additionally, comparative expression profilings of untreated versus interferon (IFN)-γ-treated RCC cell lines were performed applying qRT-PCR, Western blot and/or flow cytometry.

NAD(P)H:quinone oxidoreductase 1 (NQO1) P187S polymorphism and prostate cancer risk in Caucasians.

NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1(609)TT genotype, and low to intermediate activity was detected in NQO1(609)CT genotype compared with (609)CC genotype.

Enhanced expression of peroxisome proliferate-activated receptor gamma (PPAR-γ) in advanced prostate cancer.

Background: Recent studies have underlined the role of nuclear receptors in the involvement of prostate cancer signalling pathways.

Patients And Methods: A total of 84 benign prostate hyperplasia (BPH), 84 low risk prostate cancer (LPC) and 64 advanced disease (APC) cases were sampled on a tissue microarray (TMA) and stained for retinoic acid receptor (RAR)-α, retionoid X receptor (RXR)-α, liver X receptor (LXR)-α, farnesoid X receptor (FXR) and proliferate-activated receptor gamma (PPAR)-γ and the (pro)-inflammatory molecules cyclooxygenase 2 (COX2), tumor necrosis factor (TNF)-α and inducible Nitric oxide synthase (iNOS) immunohistochemically.

Results: PPAR-γ expression in APC tissues was found to be significantly higher than that in LPC and BPH specimens (p<0.

Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three main subtypes of sporadic renal cell carcinoma.

Objectives: We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC).

Methods: Expression of MMR proteins hMLH1 and hMSH2 were investigated in 166 RCC tumors, containing the main subtypes by immunohistochemistry. Furthermore, each tumor was screened for microsatellite instability (MSI) using the National Cancer Institute consensus panel for hereditary non-polyposis colon carcinoma as well as for elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) by 10 additional markers.

Immunohistochemical marker panel differentiates between the three most common subtypes of renal cell carcinoma independent from histomorphologic criteria.

To develop a reliable immunohistochemical marker panel differentiating between the three most common renal cell carcinoma (RCC) subtypes without inclusion of histomorphologic criteria we investigated protein expression of vimentin, glutathione S-transferase alpha (GST-α), CD10, CD117 (C-KIT), carbonic anhydrase 2 (CAII), parvalbumin, alpha-methyl-CoA-racemase (AMACR), and cytokeratin-19 (CK 19) in 65 age and stage matched trios of clear cell carcinoma, papillary renal carcinoma and chromophobe renal carcinoma using tissue microarrays. All markers displayed significant differential expression among the subtypes (p < 0.001) except CAII (p = 0.

Mutational activation of FGFR3: no involvement in the development of renal cell carcinoma.

Background: Somatic point mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been identified in certain types of urological cancers, especially urothelial carcinoma of the bladder and the renal pelvis, and could be correlated with a favourable outcome. However, comprehensive data on the FGFR3 mutation status in renal cell carcinoma (RCC) are still missing.

Methods: In order to investigate a possible role for FGFR3 mutations in renal cell carcinogenesis, we performed a sequence-based mutational analysis of FGFR3 in 238 primary RCC.

PAX8 is expressed in the majority of renal epithelial neoplasms: an immunohistochemical study of 223 cases using a mouse monoclonal antibody.

Aims: PAX8 is a cell lineage-specific transcription factor which plays a crucial role in the organogenesis of the kidney, thyroid gland and Müllerian duct. A previous study showed that PAX8 is a specific and sensitive marker for both renal and ovarian carcinomas. The purpose of this study is to investigate PAX8 expression using a new monoclonal PAX8 antibody in a larger number of renal epithelial neoplasms including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma and renal oncocytoma.

Analysis of bronchoalveolar lavage from human lung transplant recipients by flow cytometry.

Bronchoalveolar lavage (BAL) cells and peripheral blood leucocytes (PBL) from 24 lung transplant recipients were analysed for leucocyte subsets and expression of cell surface antigens. Total and differential white cell counts were performed on BAL, and lymphocyte subsets were evaluated in both BAL and peripheral blood. Measurement of immunofluorescence by flow cytometry was used to assess the percentage of: T cells (CD3+); T-helper cells (CD4+); T-cytotoxic/suppressor cells (CD8+); and activated lymphocytes (HLA-DR+).

Cytokine gene expression in human lung transplant recipients.

The polymerase chain reaction was used to evaluate cytokine gene expression in bronchoalveolar lavage (BAL) cells and peripheral blood leukocytes in 31 human lung transplant recipients. All patients were maintained on a triple immunosuppression regimen consisting of CsA, AZA, and prednisone. Posttransplant survival ranged from 0.

The diagnosis of obliterative bronchiolitis after heart-lung and lung transplantation: low yield of transbronchial lung biopsy.

Obliterative bronchiolitis is the most significant long-term complication of lung and heart-lung transplantation characterized by the rapid development of obstructive airway disease. It is thought to be a manifestation of chronic rejection and has been treated, with limited success, with augmentation of immunosuppression. Early detection of obliterative bronchiolitis and prompt initiation of therapy may result in an improved outcome.

Diagnosis of bronchiolitis obliterans in heart-lung transplantation patients: importance of bronchial dilatation on CT.

Objective: The purpose of this study was to evaluate the significance of bronchial dilatation identified on high-resolution CT scans obtained after heart-lung transplantation. Bronchial dilatation has been identified on pathologic specimens and on high-resolution CT scans of patients with severe bronchiolitis obliterans after lung transplantation, but this finding has not previously been systematically studied as a manifestation of this complication.

Materials And Methods: We studied the high-resolution CT scans of 16 patients who had had heart and lung transplantation at least 1 year before, and compared the percentage of dilated bronchi with evidence of small airways disease shown on pulmonary function tests.

Cystic fibrosis. Target population for lung transplantation in North America in the 1990s.

Cystic fibrosis is the most common lethal genetic disease occurring in the white population. It is estimated that 3.5% of the 20,000 individuals with cystic fibrosis in North America will die each year of end-stage lung disease.